Intestinal Microbiota Influence Doxorubicin Responsiveness in Triple-Negative Breast Cancer

Bawaneh, Alaa; Wilson, Ana; Levi, Nicole; Howard-McNatt, Marissa; Chiba, Akiko; Soto-Pantoja, David R.; Cook, Katherine L.

doi:10.3390/cancers14194849

Cited by 17 publications

(22 citation statements)

References 66 publications

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“…Moreover, the introduction of a high-fat diet-FMT notably alters the gut microbiome, which, subsequently, decreases the responsiveness of these mice toward doxorubicin efficacy. Together, the findings denote that modulation of the gut microbiota can drastically influence chemotherapy responsiveness in the TNBC animal model 75 . A recent study demonstrated that the microbial composition of patient stool samples prior to treatment is comprised of Firmicutes and Bacteroidetes as the prevalent phyla.…”

Section: Alterations In the Gut Microbiota Impact Therapeutic Respons...mentioning

confidence: 73%

The gut microbiota in breast cancer development and treatment: The good, the bad, and the useful!

2023

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Regardless of the global progress in early diagnosis and novel therapeutic regimens, breast carcinoma poses a devastating threat, and the advances are somewhat marred by high mortality rates. Breast cancer risk prediction models based on the known risk factors are extremely useful, but a large number of breast cancers develop in women with no/low known risk. The gut microbiome exerts a profound impact on the host health and physiology and has emerged as a pivotal frontier in breast cancer pathogenesis. Progress in metagenomic analysis has enabled the identification of specific changes in the host microbial signature. In this review, we discuss the microbial and metabolomic changes associated with breast cancer initiation and metastatic progression. We summarize the bidirectional impact of various breast cancer-related therapies on gut microbiota and vice-versa. Finally, we discuss the strategies to modulate the gut microbiota toward a more favorable state that confers anticancer effects.

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Section: Alterations In the Gut Microbiota Impact Therapeutic Respons...mentioning

confidence: 73%

The gut microbiota in breast cancer development and treatment: The good, the bad, and the useful!

2023

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“…However, as anthracycline antibiotic, DOX might affect the abundance of gut microbiota. In some other animal models induced by DOX, the decrease of intestinal flora abundance was also observed ( Bawaneh et al, 2022 ; Huang et al, 2022 ). However, we found that MCD rat model are still established successfully after gut microbial cleaning, which indicated that DOX did not induce MCD through gut microbiota.…”

Section: Discussionmentioning

confidence: 87%

Characterization and diagnostic value of the gut microbial composition in patients with minimal change disease

et al. 2022

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Background: Minimal change disease (MCD) is one of the most common causes of primary nephrotic syndrome with high morbidity. This study aimed to explore the typical alterations of gut microbiota in MCD and establish a non-invasive classifier using key gut microbiome. We also aimed to evaluate the therapeutic efficiency of gut microbiota intervention in MCD through animal experiments.Methods: A total of 222 stool samples were collected from MCD patients and healthy controls at the First Affiliated Hospital of Zhengzhou University and Shandong Provincial Hospital for 16S rRNA sequencing. Optimum operational taxonomic units (OTUs) were obtained for constructing a diagnostic model. MCD rat models were established using doxorubicin hydrochloride for exploring the therapeutic efficiency of gut microbial intervention through fecal microbiota transplantation (FMT).Results: The α-diversity of gut microbiota decreased in MCD patients when compared with healthy controls. The relative abundance of bacterial species also changed significantly. We constructed a diagnostic model based on eight optimal OTUs and it achieved efficiency of 97.81% in discovery cohort. The high efficiency of diagnostic model was also validated in the patients with different disease states and cross-regional cohorts. The treatment partially recovered the gut microbial dysbiosis in patients with MCD. In animal experiments, likewise, the gut microbiota changed sharply in MCD rats. However, gut microbial interventions did not reduce urinary protein or pathological kidney damage.Conclusion: Gut Microbiota shifts sharply in both patients and rats with MCD. Typical microbial changes can be used as biomarkers for MCD diagnosis. The gut microbiota compositions in patients with MCD tended to normalize after treatment. However, the intervention of gut microbiota seems to have no therapeutic effect on MCD.

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“…Interestingly, microbes residing in organs distant from the breast are also associated with the occurrence of breast cancer through diverse mechanisms. Specifically, the gut microbiome is capable of differentially altering the incidence of steroid hormone receptor‐positive 85 and ‐negative 86 breast cancer. The abundance and composition of the gut microbiota have been shown to affect: (i) the concentration of circulating steroid hormones; (ii) interaction of microbiome with the gut–brain axis that has a strong correlation with hormonal regulation; (iii) levels of metabolites of the gut microbiota with tumorigenic or antitumorigenic potential; and (iv) crosstalk of gut microbiome with immune system as it is an important effector of immune response and inflammation 23 .…”

Section: Influence Of Gut Microbiome Composition On Incidence and Pro...mentioning

confidence: 99%

“…A recent study by Vernaci et al suggested that patients with TNBC that respond to anthracycline‐based chemotherapy have a higher α‐diversity and higher species richness than patients that relapse 95 . Further, Bawaneh et al showed that administration of doxorubicin alters the composition of the gut microbiome, and this or high‐fat diet‐derived fecal microbiota transplantation reduces the chemotherapeutic efficacy of doxorubicin 86 . Moreover, the anticancer drugs alter the composition of the gut microbiome in mice, and germ‐free mice or those pretreated with antibiotics show resistance to anticancer agents, such cyclophosphamide 96 .…”

Section: Influence Of Gut Microbiome Composition On Treatment Outcome...mentioning

confidence: 99%

Gut microbiome influences incidence and outcomes of breast cancer by regulating levels and activity of steroid hormones in women

2023

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BackgroundBreast cancer, the leading cancer type in women worldwide, is affected by reproductive and nonreproductive factors. Estrogen and progesterone influence the incidence and progression of breast cancer. The microbiome of the gut, a complex organ that plays a vital role in digestion and homeostasis, enhances availability of estrogen and progesterone in the host. Thus, an altered gut microbiome may influence the hormone‐induced breast cancer incidence. This review describes the current understanding of the roles of gut microbiome in influencing the incidence and progression of breast cancer, with an emphasis on the microbiome‐induced metabolism of estrogen and progesterone.Recent FindingsMicrobiome has been recognized as a promising hallmark of cancer. Next‐generation sequencing technologies have aided in rapid identification of components of the gut microbiome that are capable of metabolizing estrogen and progesterone. Moreover, studies have indicated a wider role of the gut microbiome in metabolizing chemotherapeutic and hormonal therapy agents and reducing their efficacy in patients with breast cancer, with a predominant effect in postmenopausal women.ConclusionThe gut microbiome and variations in its composition significantly alter the incidence and therapy outcomes of patients with breast cancer. Thus, a healthy and diverse microbiome is required for better response to anticancer therapies. Finally, the review emphasizes the requirement of studies to elucidate mechanisms that may aid in improving the gut microbiome composition, and hence, survival outcomes of patients with breast cancer.

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Intestinal Microbiota Influence Doxorubicin Responsiveness in Triple-Negative Breast Cancer

Cited by 17 publications

References 66 publications

The gut microbiota in breast cancer development and treatment: The good, the bad, and the useful!

The gut microbiota in breast cancer development and treatment: The good, the bad, and the useful!

Characterization and diagnostic value of the gut microbial composition in patients with minimal change disease

Gut microbiome influences incidence and outcomes of breast cancer by regulating levels and activity of steroid hormones in women

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